A roadmap to develop dementia research capacity and capability in Pakistan: a model for low- and middle-income countries

Objective To produce a strategic roadmap for supporting the development of dementia research in Pakistan. Background While global research strategies for dementia research already exist, none is tailored to the specific needs and challenges of low- and middle-income countries (LMIC) like Pakistan. Methods We undertook an iterative consensus process with lay and professional experts to develop a Theory of Change-based strategy for dementia research in Pakistan. This included Expert Reference Groups (ERGs), strategic planning techniques, a “research question” priority survey, and consultations with Key Opinion Leaders. Results We agreed on ten principles to guide dementia research in Pakistan, emphasizing pragmatic, resource sparing, real-world approaches to support people with dementia, both locally and internationally. Goals included capacity/capability building. Priority research topics included raising awareness and understanding of dementia, and improving quality of life. Conclusion This roadmap may be a model for other LMIC health ecosystems with emerging dementia research cultures

Evaluation of Marginal and Internal Fit of Ceramic Laminate Veneers Fabricated with Five Intraoral Scanners and Indirect Digitization.

The long-term success of ceramic laminate veneers (CLVs) is influenced by the marginal and internal fit of the restorations. However, studies comparing the fit of CLVs using different intraoral scanners or the indirect digitization technique are lacking. The purpose of this study was therefore to assess the marginal and internal fit of CAD/CAM-milled CLVs using different intraoral scanners and the indirect digitalization technique. An ivorine typodont maxillary left-central incisor was prepared; the tooth and the neighboring teeth were scanned and used as a template to print ninety 3D partial models. Thereafter, ceramic laminate veneers (CLVs) (N = 90) were milled from IPS-Emax CAD blocks and divided into six equal groups (15 specimens each) according to the type of intraoral scanner (IOS), as follows: Omnicam IOS, SC3600 IOS, Trios 3 IOS, Emerald IOS, I500 IOS. Fifteen further CLVs were fabricated using the conventional indirect digitalization technique. After cementation on the resin dies and embedding in clear epoxy resin, specimens were sectioned inciso-gingivally and mesio-distally. At the incisal and cervical positions, the marginal discrepancy was measured and evaluated in addition to the internal gap at six locations using SEM (200×). Differences between gap measurements among the six groups were determined using ANOVA. Games-Howell multiple comparisons for homogenous variances and LSD multiple comparisons for non-homogenous variances were used with 95% confidence intervals. The significance level was set at 0.05. The lowest mean absolute marginal gap at the incisal margins (AMGI) was recorded for Omnicam group (203.28 ± 80.14) µm, while the highest mean absolute marginal gap at the cervical margins (AMGC) was recorded for Omnicam group (147.16 ± 59.78) µm. The mean AMGC was reported to be significantly different between the conventional technique (146.75 ± 38.43) µm and Trios 3 (91.86 ± (35.51) µm; p = 0.001) and between Emerald (112.37 ± (50.31) µm; p = 0.042) and I500 (86.95 ± (41.55) µm; p 0.05). Marginal gaps were higher in the incisal region compared to the cervical region with both the indirect digitization technique and the IOSs. Ceramic laminate veneers (CLVs) fabricated using IOSs produced overall internal and marginal fit adaptation results comparable to CLVs fabricated from the indirect digitalization method, and both techniques produced clinically acceptable results

Rilonacept and Anakinra in Recurrent Pericarditis: A Systematic Review and Meta-Analysis

Interleukin 1 (IL-1) has been indicated as a mediator of recurrent pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing interleukin 1 alpha (IL-1α) and interleukin 1 beta (IL-1β), has demonstrated promising results in a phase II study in recurrent or refractory pericarditis. Anakinra is a recombinant inhibitor of the IL-1 receptor with a demonstrated reduction in the incidence of recurrent pericarditis. Definite pharmacological management of pericarditis is key to preventing recurrences, mostly treatment options for recurrent pericarditis refractory to conventional drugs. Here we critically discuss the existing therapy options for recurrent pericarditis, with a focus on new pharmacological approaches: rilonacept and anakinra. A systematic search was conducted across online databases such as PubMed, Cochrane, Google Scholar, ScienceDirect, CINAHL, Scopus, and Embase to obtain clinical trials that assess the effectiveness of anti-interleukin 1 therapy such as anakinra and rilonacept in the management of recurrent pericarditis. Our study concluded that anti-interleukin 1 therapy significantly improved both the quality of life and the clinical outcomes of the study population. These outcomes were most prominent with the use of rilonacept and anakinra in the trial treatment. Rilonacept and anakinra are valuable options in case of recurrent pericarditis refractory to conventional drugs

Neural signatures of hyperdirect pathway activity in Parkinson’s disease

Parkinson’s disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21–30 Hz) but not low (13-21 Hz) beta frequency range correlated with ‘hyperdirect pathway’ fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD

Noncommutative Electromagnetism As A Large N Gauge Theory

We map noncommutative (NC) U(1) gauge theory on R^d_C X R^{2n}_{NC} to U(N -> \infty) Yang-Mills theory on R^d_C, where R^d_C is a d-dimensional commutative spacetime while R^{2n}_{NC} is a 2n-dimensional NC space. The resulting U(N) Yang-Mills theory on R^d_C is equivalent to that obtained by the dimensional reduction of (d+2n)-dimensional U(N) Yang-Mills theory onto R^d_C. We show that the gauge-Higgs system (A_\mu,\Phi^a) in the U(N -> \infty) Yang-Mills theory on R^d_C leads to an emergent geometry in the (d+2n)-dimensional spacetime whose metric was determined by Ward a long time ago. In particular, the 10-dimensional gravity for d=4 and n=3 corresponds to the emergent geometry arising from the 4-dimensional N=4 vector multiplet in the AdS/CFT duality. We further elucidate the emergent gravity by showing that the gauge-Higgs system (A_\mu,\Phi^a) in half-BPS configurations describes self-dual Einstein gravity.Comment: 25 pages; More clarifications, to appear in Eur. Phys. J.

GLP-1R Agonist Liraglutide Activates Cytoprotective Pathways and Improves Outcomes After Experimental Myocardial Infarction in Mice

OBJECTIVE—Glucagon-like peptide-1 receptor (GLP-1R) ago-nists are used to treat type 2 diabetes, and transient GLP-1 administration improved cardiac function in humans after acute myocardial infarction (MI) and percutaneous revascularization. However, the consequences of GLP-1R activation before isch-emic myocardial injury remain unclear. RESEARCH DESIGN AND METHODS—We assessed the pathophysiology and outcome of coronary artery occlusion in normal and diabetic mice pretreated with the GLP-1R agonist liraglutide. RESULTS—Male C57BL/6 mice were treated twice daily for 7 days with liraglutide or saline followed by induction of MI. Survival was significantly higher in liraglutide-treated mice. Lira-glutide reduced cardiac rupture (12 of 60 versus 46 of 60; P 0.0001) and infarct size (21 2 % versus 29 3%, P 0.02) an